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Effects of Omega-3 Fatty Acid on Endotoxin-induced Acute Lung Injury in Rabbits
Biomed Sci Letters 2021;27:19-27
Published online March 31, 2021;  https://doi.org/10.15616/BSL.2021.27.1.19
© 2021 The Korean Society For Biomedical Laboratory Sciences.

Eun-A Jang*, Sung-Kuk Son*, Jeong-Hyeon Kang*, Seongheon Lee* * and Sang-Hyun Kwak,* *

Department of Anesthesiology and Pain Medicine Chonnam National University Medical School & Hospital, Gwangju 61469, Korea
Correspondence to: Sang-Hyun Kwak. Department of Anesthesiology and Pain Medicine Chonnam National University Medical School & Hospital, 42 Jebong Ro, Donggu, Gwangju 61469, Korea.
Tel: +82-62-220-6893, Fax: +82-62-232-6294, e-mail: shkwak@jnu.ac.kr
*Post-Doctor, **Professor.
Received December 12, 2020; Revised March 2, 2021; Accepted March 3, 2021.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
This study was undertaken to clarify the effects of omega-3 fatty acid on endotoxin-induced acute lung injury. Rabbits were randomly assigned to one of four groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, omegaven infuison (0.5 mL/kg/hr) and endotoxin, lipoven (0.5 mL/kg/hr) and endotoxin respectively. Infusion of saline was started 0.5 hr before the infusion of saline or endotoxin, and omegaven and lipoven were started 2 hours after endotoxin infusion for 4 hours. The lungs of rabbits were ventilated with 40% oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and peripheral blood leukocyte were recorded. The wet/dry (W/D) weight ratio of lung and lung injury score were measured, and analysis of bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and peripheral blood leukocyte and platelet count. And it increased W/D ratio of lung, lung injury score and leukocyte count, percentage of PMN cells, concentration of IL-8 in BALF. Omegaven attenuated all these changes except for peripheral blood leukocyte counts. Omegaven attenuated endotoxin-induced acute lung injury in rabbits mainly by inhibiting neutrophil and IL-8 responses, which may play a central role in endotoxin-related lung injury.
Keywords : Acute lung injury, Endotoxins, Systemic inflammatory response syndrome, Omegaven
꽌 濡

湲됱꽦 샇씉 怨ㅻ 利앺썑援곗 湲됱꽦 뿼利, 誘몄꽭 삁愿 넀긽 諛 利앷 맂 룓 삁愿 諛 긽뵾 닾怨쇱꽦쓣 룷븿븯뒗 蹂듯빀쟻씤 엫긽 利앺썑援곗씠떎(Kollef and Schuster, 1995). 移섎즺쓽 諛쒕떖뿉룄 遺덇뎄븯怨, 쁽옱룄 뿬쟾엳 40% 씠긽쓽 넂 궗留앸쪧쓣 蹂댁씠怨 엳떎(Maca et al., 2017). 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗쓽 媛옣 쓷븳 썝씤 뙣삁利앹씠씪怨 븣젮졇 엳떎(Knaus et al., 1994; Wheeler and Bernard, 2007). 뙣삁利앹쑝濡 씤븳 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗쓽 젙솗븳 諛쒕퀝 湲곗쟾 븘吏 諛앺吏吏 븡븯吏留, 룓 궡 以묒꽦援ъ쓽 怨쇰룄븳 異뺤쟻, Tumor necrosis factor-慣 (TNF-慣), Interleukin (IL)-1, IL-6, IL-8 媛숈 쟾뿼利앹꽦 궗씠넗移댁씤(Proinflammatory cytokine)쓽 利앷 벑씠 二쇱슂 듅吏뺤씠硫 씠윭븳 留ㅺ컻臾쇰뱾씠 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗쓽 떆옉怨 吏꾪뻾뿉 以묒슂븳 뿭븷쓣 븳떎怨 븣젮졇 엳떎(Jacobs et al., 1989; Suter et al., 1992; Chollet-Martin et al., 1996; Goodman et al., 1996). 룓 궡뿉꽌쓽 以묒꽦援ъ쓽 솢꽦솕濡 씤빐 誘몄꽭 삁愿 넀긽씠 씪뼱굹怨, 以묒꽦援 떒諛깅텇빐슚냼(Protease) 諛섏쓳꽦 궛냼醫(Reactive oxygen species)씠 遺꾨퉬맂떎(McCord et al., 1994; Okumura et al., 1995). 洹 以 IL-8 빆-IL-8 옄媛삎泥댁쓽 삎꽦쓣 넻빐꽌 媛뺣젰븯寃 샇以묎뎄 쑀씤 諛 솢꽦솕瑜 떆궎怨, IL-8 蹂듯빀泥대뒗 Fc款RII慣 닔슜泥댁쓽 긽샇 옉슜쓣 넻빐 湲됱꽦 룓 넀긽쓽 諛쒖깮뿉 以묒슂븳 뿭븷쓣 븳떎(Allen and Kurdowska, 2014).

Eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), 慣-linolenic acid (ALA) 벑쓽 삤硫붽-3 吏諛⑹궛 떎媛쓽 遺덊룷솕 吏諛⑹궛쑝濡 씤泥댁뿉 쑀슜븳 떎뼇븳 슚怨쇨 諛앺졇 엳떎. 洹 슚怨쇰 궡렣蹂대㈃, 以묒꽦吏諛⑹쓣 以꾩씠怨, High density lipoprotein (HDL) 肄쒕젅뒪뀒濡ㅼ쓣 利앷떆耳 怨좎삁利앹쓣 삁諛⑺븯怨(Maki et al., 2013), 쟾떊 삁愿 빆쓣 媛먯냼떆耳 삁븬쓣 궙異붾ʼn(Miller et al., 2014), 뿀삁꽦 빆 遺젙留 슚怨(Pignier et al., 2007), 愿긽 룞留 떖옣 吏덊솚 솚옄쓽 떖洹 寃쎌깋 諛 떖옣 吏덊솚쑝濡 씤븳 궗留앹쓣 媛먯냼떆궎뒗(Bucher et al., 2002) 벑쓽 슚怨쇰 굹궡뿀떎. 쑀諛⑹븫, 옣븫, 쟾由쎌꽑븫뿉 븳 빆븫 슚怨 諛(de Deckere, 1999; Augustsson et al., 2003) 슦슱利, 遺덉븞, 뙆궓뒯蹂 媛숈 젙떊 吏덊솚뿉 븳 슚怨쇨 諛앺졇 엳떎(Naliwaiko et al., 2004; Green et al., 2006; Bousquet et al., 2008). 삉븳 瑜섎쭏떚뒪 愿젅뿼 媛숈 留뚯꽦 뿼利앹뿉룄 빆뿼利 슚怨쇨 엳떎怨 諛앺졇 엳떎(Fortin et al., 1995).

삤硫붽-3쓽 씠윭븳 슚怨쇰뱾 以 빆뿼利 슚怨쇰뒗 떎뼇븳 硫붿빱땲利섏뿉 쓽빐 굹굹硫 씠윭븳 옉슜뱾 꽭룷留됱쓽 吏諛⑹궛 援ъ꽦쓽 蹂솕 愿젴씠 엳떎. 꽭룷留됱쓽 援ъ꽦臾쇱쓽 蹂솕뒗 꽭룷留됱쓽 쑀룞꽦, 蹂寃쎈맂 쑀쟾옄 諛쒗쁽쑝濡 씠뼱吏뒗 꽭룷 떊샇 쟾떖 泥닿퀎, 吏吏 留ㅺ컻泥 깮궛 벑쓣 議곗젙븷 닔 엳떎(Calder, 2010). 빆뿼利 옉슜뿉 븳 떎뼇븳 삤硫붽-3 옉슜 以 뿼利 遺쐞뿉꽌 諛⑹텧릺뒗 솕븰臾쇱쭏뿉 諛섏쓳븯뿬 諛깊삁援ш 뿼利 솢꽦솕 遺쐞濡 씠룞븯뒗 怨쇱젙씤 諛깊삁援ъ쓽 二쇳솕꽦(Chemotaxis)怨 쑀궗븳 꽦뼢쓽 옉슜씠 엳떎(Lewis et al., 1990; Schmidt et al., 1991). 씠븣 뿼利 遺쐞뿉꽌 諛⑹텧릺뒗 솕븰臾쇱쭏쓣 솕븰쑀씤臾쇱쭏(chemo-attractants)씠씪 씠由 遺瑜대ʼn, Arachidonic acid뿉꽌 뙆깮릺뒗 Leukotriene B4媛 룷븿맂떎. 洹 湲곗쟾씠 븘吏곸 紐낇솗븯吏 븡쑝굹 솕븰쑀씤臾쇱쭏 愿젴맂 닔슜泥댁뿉 븳 湲명빆 옉슜 삉뒗 諛쒗쁽媛먯냼뿉 쁺뼢쓣 誘몄튌 寃껋쑝濡 삁痢〓릺湲곗뿉(Lewis et al., 1990; Schmidt et al., 1991; Sperling et al., 1993; Calder, 2013), 슦由щ뒗 Endotoxin쑝濡 쑀諛쒕맂 湲됱꽦 룓 넀긽뿉 삤硫붽-3 吏諛⑹궛씠 뭾遺븳 吏諛 쑀젣씤 Omegaven쓽 솕븰쑀씤臾쇱쭏怨 愿젴맂 빆뿼利 슚怨쇰 븣븘蹂닿퀬옄 븯떎.

긽 諛 諛⑸쾿

떎뿕 룞臾

2.0~2.5 kg쓽 닔而 諛깆깋 넗겮(Damul science, 쟾)瑜 궗슜븯떎. 떎뿕 룞臾쇱 쓬떇怨 臾쇱뿉 옄쑀濡寃 젒洹쇳븷 닔 엳뿀쑝硫, 12떆媛꾩쓽 궙怨 諛ㅼ쓽 닚솚쓣 쑀吏븯떎. 紐⑤뱺 떎뿕 엫긽뿰援ъ떖쓽 쐞썝쉶쓽 듅씤 썑(CNU-IACUC-H-2015-27) 떆뻾릺뿀떎.

떎뿕 諛⑸쾿

癒쇱 떎뿕 룞臾쇰뱾쓣 Ketamine hydrochloride (30 mg/kg)怨 Xylazin hydrochloride (0.3 mg/kg)쑝濡 留덉랬븳 썑 닔븸怨 빟臾쇱쓽 吏냽쟻 二쇱엯쓣 쐞빐 洹쓽 씠 젙留μ뿉 移댄뀒꽣瑜 궫엯븯떎. 씠 젙留κ쓣 넻빐 떎뿕씠 걹궇 븣源뚯 Lactated Ringer's solution쓣 8 mL/kg/hr쓽 냽룄濡 닾뿬븯떎. 옄諛쒗샇씉 긽깭뿉꽌 湲곌젅媛(tracheostomy)瑜 臾닿퇏쟻쑝濡 떆뻾 썑 湲곌 궡 궫愿븯怨(3.5-mm 而ㅽ봽 뾾뒗 뒠釉), 留덉랬쓽 쑀吏 洹 씠셿쓣 쐞빐 Ketamine (3 mg/kg/hr)怨 Vecuronium bromide (0.05 mg/kg/hr)瑜 吏냽 二쇱엯븯떎. 湲곌퀎 솚湲곌린(Servo 900B, Siemen-Elema, Solna, Sweden)瑜 씠슜븯뿬 떎뿕 룞臾쇱쓽 룓瑜 湲곌퀎 솚湲고븯떎(씉湲곗븬 15 cmH2O, 샇湲곕쭚뼇븬 3 cmH2O, 궛냼 냽룄 40%, I:E ratio 1:2) 샇씉닔뒗 씠궛솕깂냼遺꾩븬(PaCO2)씠 35~50 mmHg쑝濡 쑀吏릺룄濡 議곗젅븯떎.

떎뿕 룞臾쇱쓽 泥댁삩쑀吏瑜 쐞빐 떇룄 삩룄瑜 36.5꼦뿉꽌 37.5꼦濡 쑀吏븯룄濡 쟾湲 떞슂뿉 늻씠怨, 媛뿴 벑쑝濡 鍮꾩떠二쇱뿀떎. 吏냽쟻씤 룞留μ븬쓽 媛먯떆 룞留ν삁 寃궗瑜 쐞빐 寃쎈룞留μ쓣 넻빐 룞留μ쑝濡 移댄뀒꽣瑜 궫엯븯떎.

湲곗큹媛 痢≪젙 썑, 떎뿕 룞臾쇱쓣 臾댁옉쐞濡 꽕 洹몃9쑝濡 굹늻뿀떎; 泥 踰덉㎏뒗 Saline留 닾뿬븳 S-S 洹몃9(n=7), 몢 踰덉㎏뒗 30遺꾧컙 Saline 닾뿬 썑, 30遺꾧컙 Escherichia coli endotoxin 0111:B4 (from Sigma Chem Co., St. Louis, Mo, U.S.A.)쓣 5 mg/kg쑝濡 닾뿬븳 S-E 洹몃9(n=7), 꽭 踰덉㎏뒗 30遺꾧컙 떇뿼닔 닾뿬 썑, Endotoxin쓣 30遺꾧컙 닾뿬븳 썑, Endotoxin 닾뿬 떆옉 떆젏쑝濡쒕꽣 2떆媛꾩㎏遺꽣 삤硫붽-3 吏諛⑹궛씠 뭾遺븳 Omegaven쓣 0.5 mL/kg/hr濡 4떆媛 룞븞 닾뿬븳 E-O 洹몃9(n=7), 留덉留 꽕 踰덉㎏뒗 Endotoxin 닾뿬 2떆媛꾩㎏遺꽣 삤硫붽-6 吏諛⑹궛씠 뭾遺븳 Lipoven쓣 0.5 mL/kg/hr濡 4떆媛 룞븞 닾뿬븳 E-L 洹몃9(n=7)쑝濡 굹늻뿀떎. S-S 洹몃9怨 S-E 洹몃9 Lipoven怨 Omegaven 媛숈 슜웾쓽 Saline쓣 닾뿬븯떎. 紐⑤뱺 洹몃9 Endotoxin 닾뿬 떆젏遺꽣 6떆媛꾧퉴吏 Saline씠굹 떎뿕빟臾쇱쓣 닾뿬븯떎(Fig. 1).

Fig. 1. Experimental group design. Each group received saline infusion for the first 30 minutes. S-S group received saline only throughout the study. S-E group received endotoxin for 30 minutes before and after saline infusion. E-O group and E-L group received Omegaven and Lipoven for 4 hours, respectively (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

룞留ν삁 媛뒪 遺꾩꽍怨 諛깊삁援ъ 삁냼뙋닔쓽 痢≪젙쓣 쐞빐 Saline굹 Endotoxin 닾뿬 30遺 쟾, 닾뿬 떆, 닾뿬 썑 1, 2, 3, 4, 5, 6떆媛꾩뿉 룞留ν삁 梨꾩랬瑜 떆뻾븯떎. Saline굹 Endotoxin 닾뿬 6떆媛 썑 떎뿕 룞臾쇰뱾 移섏삤렂깉 怨쇰웾 닾뿬濡 씗깮떆耳곕떎. 洹 吏곹썑 넗겮쓽 쓨怨쎌쓣 뿴뼱꽌 룓瑜 씪愿꾩쟻쑝濡 젣嫄고븯뿬 醫뚯륫 룓 긽뿽 wet-dry weight ratio瑜 痢≪젙븯怨, 醫뚯륫 룓 븯뿽 룓 넀긽 젏닔(lung injury score), 슦痢 룓뒗 湲곌吏룓룷꽭泥숈븸(Bronchoalveolar lavage fluid, BALF)쓽 諛깊삁援ъ닔 떎빑샇以묎뎄쓽 諛깅텇쑉, IL-8쓽 냽룄瑜 痢≪젙븯떎.

룞留ν삁 媛뒪 遺꾩꽍 諛 留먯큹삁븸 꽭룷닔 遺꾩꽍

룞留ν삁 삁븸 媛뒪 遺꾩꽍湲(GEM Premier Plus, Instrumentation Laboratory, Lexington, MA, U.S.A.)瑜 씠슜븯뿬 룞留ν삁궛냼遺꾩븬(PaO2), 씠궛솕깂냼遺꾩븬(PaCO2), pH, 뿼湲곌낵엵(Base excess)쓣 遺꾩꽍븯떎. 留먯큹삁븸 諛깊삁援ъ닔뒗 꽭룷닔 遺꾩꽍湲(XE2100, Sysmex, Kobe, Japan)濡 痢≪젙븯떎.

Lung wet/dry weight (W/D) ratio

醫뚰룓긽뿽쓽 臾닿쾶瑜 옺 떎쓬 60꼦 삤釉먯뿉꽌 48떆媛 룞븞 嫄댁“떆궓 썑 臾닿쾶瑜 痢≪젙븯떎. 議곗쭅쓽 遺醫 젙룄瑜 룊媛븯湲 쐞빐 wet/dry weight ratio瑜 怨꾩궛븯떎.

議곗쭅븰쟻 寃궗

議곗쭅쓽 怨좎젙쓣 쐞빐 쇊븘옒湲곌吏瑜 넻븯뿬 10% Glutaraldehyde solution瑜 醫뚰븯뿽뿉 젏쟻二쇱엯븳 썑 뙆씪뿉 븿紐곗떆耳곕떎. 怨좎젙맂 썑 옒씪궦 젅렪 Hematoxylin怨 Eosin쑝濡 뿼깋븯떎. 떎뿕뿉 빐 紐⑤Ⅴ뒗 몢 紐낆쓽 愿李곗옄媛 愿묓쁽誘멸꼍쑝濡 젅렪쓣 愿李고븳 썑 룓룷쓽 슱삁, 異쒗삁, 遺醫, 怨듦린痢듦낵 삁愿踰쎌뿉 샇以묎뎄쓽 移⑥쑄怨 쓳吏묒젙룄, 룓룷踰쎌쓽 몢猿섏 쑀由ъ쭏留 삎꽦 벑쓣 醫낇빀 룊媛븯뿬, 넀긽쓽 젙룄瑜 0(넀긽뾾쓬)遺꽣 4(理쒕 넀긽)源뚯 젏닔瑜 留ㅺ꼈떎.

湲곌吏룓룷꽭泥숈븸(bronchoalveolar lavage fluid, BALF)쓽 닔吏

슦痢 룓뿉꽌 BALF瑜 닔吏묓븯떎. 슦痢 湲곌吏瑜 넻빐 35 mL쓽 떇뿼닔瑜 떎꽢 李⑤뿉 嫄몄퀜 泥쒖쿇엳 二쇱엯븯怨 쉶닔븯湲곕 諛섎났븯떎. 떇뿼닔뒗 Ethylendiamine tetraacetic acid (EDTA)-2Na瑜 룷븿븯怨 엳뿀쑝硫, 諛깊삁援ъ쓽 궗瑜 留됯린 쐞빐 4꼦濡 깋媛곸떆耳곕떎. BALF濡 꽭룷닔 꽭룷遺꾪솕瑜 遺꾩꽍븯떎.

BALF瑜 썝떖遺꾨━븯뿬 꽭룷遺꾪솕 痢≪젙쓣 쐞빐 Wright-Giemsa 뿼깋쓣 떆뻾븯떎. 꽭룷닔 遺꾩꽍湲(cell counter, XE2100, Sysmex, Kobe, Japan)濡 BALF쓽 諛깊삁援ъ닔瑜 怨꾩궛븯떎. BALF쓽 꽭룷瑜 젣嫄고븯湲 쐞빐 4꼦뿉꽌 20遺꾧컙 썝떖遺꾨━븯떎. 꽭룷媛 뾾뒗 긽痢듭븸 뿬윭 遺遺꾩쑝濡 굹늻뼱議뚯쑝硫 蹂닔 媛믩뱾쓽 痢≪젙쓣 쐞빐 -80꼦뿉꽌 蹂닿븯떎.

湲곌吏룓룷꽭泥숈븸(bronchoalveolar lavage fluid, BALF)뿉꽌쓽 IL-8 痢≪젙

IL-8쓽 냽룄뒗 슚냼硫댁뿭痢≪젙踰(ELISA, Amersham, Bucks, U.K.)쑝濡 痢≪젙븯떎.

넻怨

룓 넀긽 젏닔뒗 以묒븰媛믪쑝濡 몴쁽븯怨 굹癒몄 뜲씠꽣뒗 룊洹좉컪 짹 몴以렪李⑤줈 몴떆븯떎. 뜲씠꽣 媛믩뱾쓽 遺꾩꽍 떎以묐퉬援먮 씠슜븯떎. 뿬윭 떆媛꾩뿉 빐 痢≪젙븳 뜲씠꽣 媛믩뱾뿉 빐꽌뒗 ANOVA 寃젙 썑 Dunnett쓽 寃젙쓣 씠슜븯쑝硫, 떒씪 떆媛꾩뿉 빐 痢≪젙븳 媛믪뿉 빐꽌뒗 Student's unpaired t 寃젙쓣 씠슜븯떎. 議곗쭅븰쟻 뜲씠꽣뿉뒗 Wilcoxon U-test瑜 씠슜븯떎. P value 媛믪씠 0.05 誘몃쭔씤 寃쎌슦 쓽誘 엳뒗 寃곌낵媛믪씠씪 뙋떒븯떎.

寃 怨

떖諛뺤닔 룊洹좏삁븬쓽 삁瑜섏뿭븰 紐⑤뱺 洹몃9뿉꽌 넻怨꾩쟻 쑀쓽븳 李⑥씠瑜 蹂댁씠吏 븡븯떎. 룞留ν삁 궡쓽 씠궛솕깂냼遺꾩븬 S-E, E-O, E-L 洹몃9뿉꽌 S-S 洹몃9뿉 鍮꾪빐 利앷븯떎. 留먯큹 諛깊삁援ъ닔뒗 S-S 洹몃9怨 鍮꾧탳빐꽌 S-E, E-O, E-L 洹몃9뿉꽌 젏李⑥쟻쑝濡 媛먯냼븯떎(Table 1). 룞留ν삁궛냼遺꾩븬 S-E 洹몃9 S-S 洹몃9怨 鍮꾧탳븯뿬 젏李⑥쟻쑝濡 媛먯냼븯뒗 뼇긽쓣 蹂댁쑝硫, Omegaven 룞留ν삁궛냼遺꾩븬쓽 媛먯냼瑜 쑀쓽븯寃 媛먯냼떆耳곕떎(Fig. 2).

Changes in blood gas, hemodynamics and peripheral blood leukocytes

Variables Time after start of endotoxin or saline infusion

-0.5 0 1 2 3 4 5 6
PaCO2 (mmHg)
S-S 37±0.7 35±1 35±1.2 34±2 35±2.4 35±1.7 33±1.1 33±1.1
S-E 37±0.7 41±2.3 41±3.1 49±6.5 50±6.7 51±7.1 52±6.2 56±7
E-O 39±1.1 42±2.2 39±3.0 38±3.3 43±3.8 41±3.1 44±3.7 45±3.3
E-L 41±0.9 39±2.6 38±3.2 41±4.3 39±4.5 39±3.2 39±4.1 42±3.7
HR (bpm)
S-S 222±3 222±3 224±2 226±3 224±2 224±2 220±4.1 225±2
S-E 225±4 225±4 212±11 221±6 214±8 207±8 203±10 201±13
E-O 224±9 232±5 222±9 233±7 221±7 219±7 211±9 199±6
E-L 228±9 231±7 224±6 220±10 237±6 232±10 221±10 224±11
MBP (mmHg)
S-S 84±3 82±3 85±4 89±3 88±4 86±3 85±4 85±3
S-E 78±4 77±6 78±5 78±6 83±5 82±5 77±7 87±7
E-O 73±4 84±4 82±5 86±4 76±7 76±7 72±7 76±8
E-L 77±4 85±4 81±6 83±6 78±4 80±5 73±7 74±8
WBC (102/mm3)
S-S 44±2 47±2 44±4 48±4 49±4 48±5 44±3 45±2
S-E 52±6 50±6 26±5*† 20±3*† 16±2*† 14±2*† 13±2*† 14±2*†
E-O 47±4 46±4 23±2*† 18±3*† 15±2*† 12±1*† 12±1*† 12±1*†
E-L 52±7 49±6 27±5*† 19±3*† 15±2*† 13±2*† 11±1*† 11±2*†

*P < 0.05 vs. values of time 0 within group, †P < 0.05 vs. S-S group (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven)



Fig. 2. Partial pressure ofarterial oxygen (PaO2) changes in each study group. PaO2 decrease gradually in S-E group, compared with S-S group. Omegaven attenuate the decrease in the PaO2. *P < 0.05 vs. values of time 0 within group, †P < 0.05 vs. group S-S, ‡P < 0.05 vs. group S-E (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

Wet/dry weight ratio뒗 S-S 洹몃9怨 鍮꾧탳븯뿬 S-E 洹몃9뿉꽌 利앷븯怨, Omegaven 洹 利앷 젙룄瑜 쑀쓽븯寃 媛먯냼떆耳곕떎(Fig. 3).

Fig. 3. Comparison of wet/dry weight ratio. The wet/dry weight ratio increase in S-E group, compared with S-S group. Omegaven attenuate the increase in this ratio. *P < 0.05 vs. S-S group, †P < 0.05 vs. S-E group (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

BALF쓽 꽦遺꾨텇꽍 寃곌낵瑜 蹂대㈃ S-S 洹몃9怨 鍮꾧탳븯뿬 S-E 洹몃9뿉꽌 諛깊삁援ъ쓽 닔媛 利앷븯怨, 씠뒗 留먯큹삁븸뿉꽌 룓룷 궡濡 諛깊삁援ъ쓽 씠룞쓣 쓽誘명븯뒗뜲 Omegaven 씠 利앷 젙룄瑜 쑀쓽븯寃 媛먯냼떆耳곕떎(Fig. 4). 삉븳 S-S 洹몃9怨 鍮꾧탳븯뿬 S-E 洹몃9뿉꽌 떎빑샇以묎뎄쓽 諛깅텇쑉씠 利앷븯뒗뜲, Omegaven 씠 利앷웾쓣 쑀쓽븯寃 媛먯냼떆耳곕떎(Fig. 5).

Fig. 4. Comparison of leukocyte counts in BALF. The leukocyte counts in BALF increase in S-E group, compared with S-S group. Omegaven attenuate the increase in leukocyte counts in BALF. *P < 0.05 vs. S-S group, †P < 0.05 vs. S-E group (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

Fig. 5. Comparison of the percentage of PMNL in BLAF. The percentage of polymorphonuclear neutrophils in the BALF markedly increases in S-E group, compared with S-S group. Omegaven attenuate the increase. *P < 0.05 vs. S-S group, †P < 0.05 vs. S-E group (S-S: Saline; S-E Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

S-S 洹몃9怨 鍮꾧탳븯뿬 S-E 洹몃9뿉꽌 IL-8쓽 냽룄媛 利앷븯怨, Omegaven 씠 利앷웾쓣 쑀쓽븯寃 媛먯냼떆耳곕떎(Fig. 6).

Fig. 6. Comparison of the concentration of IL-8 in BALF. The concentration of IL-8 in the BALF increase in S-E group, compared with S-S group. Omegaven attenuate the increase. *P < 0.05 vs. S-S group, †P < 0.05 vs. S-E group, ‡P < 0.05 vs. E-L group (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

젅렪쓽 愿묓븰쁽誘멸꼍 궗吏꾩쓣 鍮꾧탳빐蹂대㈃, S-E 洹몃9뿉꽌 遺醫낃낵 異쒗삁, 룓룷踰쎌쓽 鍮꾪썑, 룓룷 怨듦컙쑝濡쒖쓽 뿼利 꽭룷쓽 移⑥쑄씠 愿李곕릺뿀怨, E-O 洹몃9뿉꽌 씠윭븳 蹂솕쓽 젙룄媛 以꾩뼱뱾뿀쓬쓣 븣 닔 엳뿀쑝硫, 룓 넀긽 젏닔瑜 鍮꾧탳븯쓣 븣룄 Omegaven 룓쓽 넀긽쓣 以꾩뿬二쇱뿀쓬쓣 븣 닔 엳떎(Fig. 7).

Fig. 7. Photomicrographic views of median value of lung injury score in (A) S-S group, (B) S-E group, (C) E-O group, (D) E-L group & (E) lung injury score. Light microscopic findings in S-E group include edema, hemorrhage, thickening of the alveolar wall, and infiltration of inflammatory cells into alveolar spaces. In contrast, these changes were less prominent in the rabbits receiving omegaven. Assessment of the lung injury scores demonstrated that omegaven successfully reduced the histopathologic severity of the lung injury (S-S: Saline; S-E: Saline-endotoxin; E-O: Endotoxin-Omegaven; E-L: Endotoxin-Lipoven).

씠긽쑝濡 遊ㅼ쓣 븣 Omegaven 룓 넀긽怨 뿰愿맂 뙣삁利앹쓽 빑떖뿭븷쓣 븳떎怨 븣젮吏 諛깊삁援ъ 쟾뿼利앹꽦 궗씠넗移댁씤씤 IL-8쓣 遺遺꾩쟻쑝濡 以꾩뿬以뚯쑝濡쒖뜥 궡룆냼뿉 쓽븳 湲됱꽦 룓 넀긽쓣 以꾩뿬以떎怨 깮媛곷맂떎.

怨 李

蹂 떎뿕쓽 二쇱슂븳 寃곌낵뒗 Omegaven씠 Endotoxin쑝濡 쑀룄맂 룓 넀긽(궛냼솕 븙솕, W/D 臾닿쾶 鍮꾩쑉, 룓 넀긽 젏닔) 젙룄瑜 媛먯냼 떆耳곌퀬, 삉븳 Endotoxin쑝濡 씤븳 뿼利앹꽦 궗씠넗移댁씤(IL-8)怨 샇以묎뎄 諛섏쓳쓣 뼲젣븯떎.

Endotoxin쑝濡 쑀룄 湲됱꽦 룓 넀긽쑝濡 씤븳 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗 샇以묎뎄 異뺤쟻, 媛꾩쭏 遺醫, 긽뵾 臾닿껐꽦쓽 뙆愿 諛 룓룷 怨듦컙쑝濡쒖쓽 떒諛깆쭏 늻異쒓낵 洹몄뿉 뵲瑜 媛뒪 援먰솚쓽 떖媛곹븳 蹂솕瑜 珥덈옒븯뒗 蹂듭옟븳 利앺썑援곗씠떎(Kollef and Schuster, 1995).

샇以묎뎄, 궗씠넗移댁씤/耳紐⑥뭅씤, 吏吏 留ㅺ컻泥(Phospholipase A2, Thromboxane A2, Prostacyclin) 諛 삁냼뙋 솢꽦솕 씤옄瑜 룷븿븳 떎뼇븳 뿼利앹꽦 留ㅺ컻泥대뱾씠 ARDS 솚옄쓽 삁븸怨 BALF뿉꽌 諛쒓껄 릺뿀떎(Demling, 1993; Touqui and Arbibe, 1999). 씠뱾 留ㅺ컻泥대뱾 湲됱꽦 룓 넀긽 諛 ARDS쓽 떆옉 諛 吏꾪뻾뿉 以묒슂븳 뿭븷쓣 븳떎.

Endotoxin TNF-慣, IL-1, IL-6 諛 IL-8怨 媛숈 궗씠넗移댁씤쓣 諛⑹텧븯뒗 룓룷 떇 꽭룷쓽 솢꽦솕瑜 쑀諛쒗븳떎. 씠 臾쇱쭏뱾 궡뵾留됱뿉꽌 젒李 遺꾩옄쓽 諛쒗쁽쓣 뼢긽떆耳 룓 삁愿 궡뵾뿉 븳 샇以묎뎄쓽 솕븰 二쇱꽦怨 遺李⑹쓣 珥됱쭊븳떎(Brigham and Meyrick, 1986; Bernard and Tedgui, 1992). 씠뒗 蹂댁껜怨꾨 솢꽦솕 떆耳 솕븰 二쇱꽦 슚怨쇱 以묒꽦援ъ쓽 異뺤쟻쓣 媛냽솕 븳떎.

遺李 遺꾩옄瑜 넻빐 룓 삁愿 궡뵾뿉 遺李⑸맂 솢꽦솕 맂 샇以묎뎄뒗 봽濡쒗뀒븘젣(Protease), 諛섏쓳꽦 궛냼醫(Reactive oxygen species) 諛 븘씪궎룉 궛 궗 궛臾(듅엳 TxA2)쓣 諛⑹텧븿쑝濡쒖뜥 궡뵾瑜 怨듦꺽븳떎. 씠 臾쇱쭏뱾 湲곌吏 닔異뺢낵 룓 삁愿 닔異뺤쓣 留ㅺ컻븯怨 룓 遺醫낆쓣 씪쑝궎뒗 紐⑥꽭 삁愿 닾怨쇱꽦쓣 利앷떆궓떎. 洹몃━怨 삁냼뙋 솢꽦솕 씤옄媛 샇以묎뎄뿉꽌 諛⑹텧릺뼱 怨좊┰맂 넗겮 룓뿉꽌 삁냼뙋 留ㅺ컻 룓 遺醫낆쓣 쑀諛쒗븳떎(Samuelsson et al., 1987; Lamy et al., 1992; Zarbock and Ley, 2009).

蹂 뿰援ъ뿉꽌 궡 룆냼 삁利앹씠 엳뒗 넗겮뿉꽌 룓쓽 W/D 鍮꾩쑉쓽 利앷, 諛 議곗쭅븰쟻 蹂솕쓽 젙룄媛 Omegaven뿉 쓽빐 媛먯냼릺뿀떎. 씠윭븳 吏몴뱾 삁愿 궡뵾 닾怨쇱꽦 옣븷濡 씤븳 룓 遺醫낆쓽 吏몴씠湲 븣臾몄뿉 以묒슂븳 諛쒓껄씠떎.

Huang, L. M. 벑 Omegaven씠 湲됱꽦 룓 넀긽씠 엳뒗 伊먯뿉꽌 IL-1棺쓽 媛먯냼 諛 룓룷 긽뵾 꽭룷쓽 꽭룷옄뿰궗瑜 以꾩엫쑝濡쒖뜥 뿼利앸컲쓳쓣 빟솕떆궡쓣 蹂닿퀬븯떎(Huang et al., 2020). 씠뒗 蹂 뿰援ъ뿉꽌쓽 Omegaven쓽 빆뿼利 슚怨쇱 씪移섑븯뒗 痢〓㈃씠 엳떎.

Mayer K 벑 寃쎌젙留 쁺뼇뿉꽌 삤硫붽-3 삤硫붽-6 吏諛 쑀젣쓽 슚怨쇰 鍮꾧탳瑜 븯떎. 삤硫붽-6媛 뭾遺븳 吏諛 쑀젣瑜 以 洹몃9뿉꽌 뜑 넂 옄쑀(free) 븘씪궎룉 궛 냽룄 諛 샇以묎뎄 湲곕뒫 넀긽쓽 媛먯냼쓣 蹂닿퀬븯뿬, 삤硫붽-3媛 뭾遺븳 吏諛 쑀젣媛 뙣삁利 솚옄뿉寃뚯꽌 뜑 씠젏씠 엳쓣 寃껋쑝濡 二쇱옣븯떎(Mayer et al., 2003). 씠뒗 蹂 끉臾몄쓽 삤硫붽-3媛 뭾遺븳 Omgeven씠 삤硫붽-6媛 뭾遺븳 Lipoven蹂대떎 빆뿼利 슚怨쇨 슦썡븯떎뒗 寃곌낵 긽넻븯뒗 痢〓㈃씠 엳떎.

Hall TC 벑 뙣삁利 以묓솚옄뱾 긽쑝濡 삤硫붽-3 吏諛⑹궛씠 뭾遺븳 쑀젣瑜 寃쎌젙留 넻빐 怨듦툒븳 寃쎌슦 닾뿬븯吏 븡 寃쎌슦瑜 鍮꾧탳븯쑝硫, 씠 鍮꾧탳뿉꽌 삤硫붽-3 吏諛⑹궛쓣 怨듦툒븳 援곗뿉꽌 삁옣 궡 吏吏 꽦遺꾩쓽 媛쒖꽑쓣 蹂 닔 엳뿀怨, 씠 寃곌낵媛 솚옄쓽 깮議댁쑉뿉 룄쓣 以 닔 엳떎怨 蹂닿퀬븯떎(Hall et al., 2016).

蹂 뿰援ъ뿉꽌 Omegaven쓣 궗슜븯吏 븡 洹몃9뿉 鍮꾪빐 Omegaven쓣 궗슜븳 洹몃9뿉꽌 BALF뿉꽌쓽 IL-8쓽 냽룄媛 쑀쓽븯寃 궙븯떎. 씠뒗 Omegaven씠 BALF 궡뿉꽌룄 궡룆냼 삁利앹뿉 쓽븳 궗씠넗移댁씤 諛섏쓳쓣 뼲젣븯뒗 슚怨쇨 엳뒗 寃껋쑝濡 蹂댁씤떎. 씠뒗 Omegaven씠 궗씠넗移댁씤 諛섏쓳 뼲젣瑜 넻븳 궛냼솕 븙솕쓽 諛⑹ 諛 룓 遺醫 빟솕뿉 슚怨쇨 엳쓬쓣 떆궗븯떎.

궡룆냼 쑀諛 룓 넀긽쓽 蹂묓깭 깮由щ뒗 蹂듭옟븯怨 씠 넀긽쓽 理쒖쥌 떒怨꾨뒗 솢꽦솕맂 諛깊삁援, 떇 꽭룷뱾씠 諛섏쓳꽦 궛냼醫, 봽濡쒗뀒븘젣, 븘씪궎룉 궛 궗臾쇱쓽 諛⑹텧濡 룓쓽 궡뵾 諛 쇅뵾 꽭룷쓽 넀긽, 넂 닾怨쇱꽦뿉 쓽븳 룓 遺醫낆씠씪 깮媛곷맂떎. 떎뼇븳 뿼利앹꽦 留ㅺ컻泥 諛 궗씠넗移댁씤뿉 쓽빐 떇 꽭룷, 以묒꽦援, 궡뵾 꽭룷 벑쓣 솢꽦솕源뚯뒗 떆媛꾩씠 븘슂븯떎. 洹몃윭誘濡 Omegaven쓽 珥덇린쓽 닾뿬媛 씠 理쒖쥌 떒怨꾩쓽 媛쒖엯쓣 넻빐 룓 넀긽쓽 빟솕뿉 룄쓣 以 닔 엳쓣 寃껋쑝濡 깮媛곷맂떎.

뙣삁利 諛 뙣삁利앹꽦 눥겕뿉 쓽븳 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗씠 엳뒗 以묓솚옄뱾 긽떦닔媛 쁺뼇 遺덇퇏삎 諛 쁺뼇 떎議곕 寃り퀬 엳떎. 씠윴 以묓솚옄뱾쓽 愿由ъ뿉꽌 媛옣 以묒슂븳 젏 以 븯굹뒗 씠 솚옄뱾뿉寃 쟻젅븳 쁺뼇 怨듦툒쓣 빐二쇰뒗 寃껋씠떎. 뙣삁利 솚옄뿉寃 쟻젅븳 쁺뼇 怨듦툒쓣 빐二쇱뼱빞 븳떎뒗 씪移섎맂 寃ы빐뒗 엳吏留 뼱뼡 쁺뼇냼 諛 꽦遺꾩쓣 怨듦툒 빐二쇱뼱빞 븯뒗吏뿉 븳 씪移섎맂 쓽寃ъ 뾾떎. Omegaven쓽 怨듦툒씠 뙣삁利앹뿉 쓽븳 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗쓣 寃り퀬 엳뒗 솚옄뿉寃뚯꽌 빆뿼利 슚怨쇰 嫄곕몮 닔 엳쓣 寃껋쑝濡 깮媛곷맂떎. 洹몃젃吏留 湲됱꽦 샇씉 怨ㅻ 利앺썑援곗쓣 媛吏 솚옄뿉寃뚯꽌 옣湲곌컙뿉 嫄몄튇 Omegaven 닾뿬쓽 슚怨쇱뿉 븳 뿰援ъ Omegaven쓽 쟻젅븳 슜웾쓣 寃곗젙븯湲 쐞븳 異붽쟻씤 뿰援ш 븘슂븯떎.

ACKNOWLEDGEMENT

None.

CONFLICT OF INTEREST

The authors have declared no conflict of interest.

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